ID 2 Quiz 1

Pneumonia Complications

Sepsis

Bacteremia

Resp. Failure

Pleural Effusion - fluid buildup

Empyema - Infection

Zosyn generic + MOA

Piperacillin-tazobactam

MOA: PBP binding/cell-wall inhibition plus beta-lactamase inhibition

Maxipime generic +MOA

Cefepime

MOA: PBP binding and cell-wall inhibition

Rocephin generic + MOA

Ceftriaxone

MOA: PBP binding and cell-wall inhibition

Unasyn generic + MOA

Ampicillin-sulbactam

MOA: Cell-wall inhibition plus beta-lactamase inhibition

Augmentin generic + MOA

Amoxicillin/Clavulanate

MOA: Cell-wall inhibition plus beta-lactamase inhibition

Levaquin generic +MOA

Levofloxacin

MOA: DNA gyrase and topoisomerase IV inhibition

CIpro generic + MOA

Ciprofloxacin

MOA: DNA gyrase and topoisomerase IV inhibition

Avelox

Moxifloxacin

MOA: DNA gyrase and topoisomerase IV inhibition

Zithromax

Azithromycin

MOA: 50S inhibition

Vibramycin

Doxycycline

MOA: 30s inhibition

Vancocin

Vancomycin

Binds D-Ala-D-Ala and inhibits cell-wall formation

Zyvox

Linezolid

MOA: Prevents formation of the 50S initiation complex

Garamycin

Gentamicin

MOA 30S binding and mRNA misreading

Nebcin

Tobramycin

MOA: 30S binding and mRNA misreading

Amikin

Amikacin

MOA: 30S binding and mRNA misreading

Ciprofloxacin Coverage

Strengths	Major gaps
Strong gram-negative and Pseudomonas activity	Weak pneumococcus, Streptococcus, and MSSA; no reliable anaerobes

Levofloxacin Coverage

Strengths	Major gaps
Pneumococcus, atypicals, gram-negatives, Pseudomonas	No reliable anaerobes or MRSA

Moxifloxacin Coverage

Strengths	Major gaps
Pneumococcus, atypicals, useful anaerobic activity	No Pseudomonas; not a UTI drug

CAP treatment + definition

Onset occurs outside of hospital

or <48 hrs after admission

(outpatient CAP - Amoxicillin 1g PO TID)

CAP microbiology

Typical - (clues COPD, Smoking, Severe strep symptoms)

• Strep Pnuem

• H Influenzae

• M Cattarhalis

Atypical (clues walking PNA)

• Mycoplasma pneum

• Chlamydophila pneum

• Legionella - cruise ship/hotel

Rare (clue recent IV antibiotics)

• MRSA

• Psuedomonas

Respiratory culture

Main use	Limitation
Organism identification and susceptibility	Negative does not rule out pneumonia

Blood culture

Main use	Limitation
Detects bacteremic infection	Low routine yield in non-severe CAP

MCR nasal PCR swab

Main use	Limitation
Helps discontinue MRSA therapy when negative	Positive does not prove MRSA pneumonia

Pneumococcal urinary antigen

Main use	Limitation
Supports narrowing	High specificity but limited sensitivity

Legionella urinary antigen

Main use	Limitation
Severe CAP or relevant exposure	Mainly detects serogroup 1

Viral PCR testing

Main use	Limitation
Identifies viral infection	Does not fully exclude bacterial coinfection

Procalcitonin

Main use	Limitation
Supports discontinuation decisions	Trend is more usedul than one value

Obtain Respiratory cultures for

• Severe CAP

• Recent IV antibiotics

• Anti-MRSA or anti-Pseudomonas treatment

• Advanced structural lung disease

High dose amoxicillin covers

Coverage: Pneumococcus

GAP: No atypicals, MRSA, or Pseudomonas

Amox-clav/cefpodoxime/cefuroxime coverage

Coverage: Pneumococcus and many H. influenzae isolates

GAP: No atypicals

Ceftriaxone/ampicillin-sulbactam coverage

Coverage: Standard inpatient typical bacteria

GAP: No atypicals/ psuedomonas

Azithromycin Coverage

Coverage: Atypicals

GAP: Pneumococcal resistance

Doxycycline Coverage

Coverage: Atypicals and typical coverage

GAP: insufficient alone for severe CAP

Levofloxacin Coverage

Coverage: Pneumococcus, atypicals, Pseudomonas

GAP: NO MRSA

Moxifloxacin Coverage

Coverage: Pneumococcus, atypicals, Anaerobes

GAP: NO PSUEDOMONAS

Cefepime/piperacillin-tazobactam

Coverage: Typical bacteria and Pseudomonas

GAP: NO atypicals or MRSA

Vancomycin/linezolid

Coverage: MRSA

GAP: No gram-negative or atypical coverage

CAP comorbidities

Fu C DAC

Functional/anatomical asplenia

Cancer

Diabetes

Alcohol Use disorder

Chronic kidney heart, or lung disease

Comobordities = Levo 750

CAP PSI/Port Score

Class III = Inpatient or outpatient observation

Class IV and V = Auto inpatient

CAP CURB 65 score

2 Inpatient or ibservtional unit

3+ inpatient

CAP Severity Assessment

Severe CAP = one major or 3 minor criteria

Major

• Septic Shock with Vasopressors

• Resp failuire w/ ventilation

Outpatient CAP treatment NO comorbidities

Preferred:

• Amoxicillin 1 g PO TID

Alternatives:

• Doxycycline 100 mg BID

• Azithromycin only if local pneumococcal resistance <25%

Outpatient CAP treatment with comorbidities

Respiratory fluoroquinolone monotherapy

• Levofloxacin 750 mg a day

• Moxifloxacin 400mg a day

OR

1 B lactam

• Amox Clav (Aug) 875/125 BID

• Cefpodoxime 200 mg BID

• Cefuroxime 500 mg BID

+ 1 atypical agent

Doxycycline 100mg BID

Azithromycin (Z-pak) 500 mg x 1 then 250mg daily

or 500mg daily for 3 days

CAP definitive therapy H influenzae

BL- negative Ampicillin/Amoxicillin

BL-positive Ceftriaxone, Amox-Clav, Cefpodoxime

CAP definitive therapy S pneumoniae

if bacteremia- Ceftriaxone or levofloxacin

CAP definitive therapy Legionella

Levofloxacin or Azithromycin

CAP definitive therapy M pneumoniae

doxycycline (Vibramycin)

CAP definitive therapy C. Pneumoniae

Azithromycin or doxycycline

CAP definitive therapy MSSA

Cefazolin (Ancef)

CAP definitive therapy MRSA

Vanc / Linezolid

CAP definitive therapy Psuedomonas

Cefepime, Pip/Tazo, levofloxacin/ciproflxacin

IV to PO transition criteria

Afebrile x24hr

Hemodynamically Stable (SBP >90)

Clinically improving with PO ability

Azithromycin Adverse effects

QT prolongation; GI upset

Amoxicillin / Amox-Clav Adverse effects

Allergy; diarrhea; C. difficile risk, greater with amox-clav

Ceftriaxone Adverse effects

C. difficile risk; biliary effects; calcium incompatibility

Cefepime adverse effects

Neurotoxicity at excessive exposure; C. difficile risk

Doxycycline adverese effects

Esophagitis; photosensitivity; GI upset; cation chelation

Lay down

Levofloxacin, Moxifloxacin Adverse effects

QT prolongation; tendon rupture; neuropathy; CNS effects; dysglycemia; aortic risk; C. difficile

Vancomycin adverse efffects

Nephrotoxicity; infusion-related flushing; need for TDM

Linezolid (Zyvox) Adverse effects

Serotonergic interaction; myelosuppression; neuropathy with longer use

Zosyn (pip/tazo) adverse effects

Allergy; diarrhea/C. difficile; renal accumulation

Standard B Lactam

Ceftriaxone 1-2g IV q24h

Atypical Coverage

Azithromycin 500mg q24h

Doxycycline 100mg IVPO q24h

Antipsuedo B. lactams

Cefepime 2g IV q8h

Pip-tazo 4.5g IV q6h

ceftazidime; meropenem; imipenem; aztreonam

Anti Psuedo FQ’s

ciprofloxacin; levofloxacin

MRSA coverage

Vanco IV

Linezolid 600mg

Inpatient CAP treatment Severe CAP

Severe =

• Respiratory failure requiring vent

• Septic shock with need of vasopressors

B lactam (unasyn/ceftriaxone) + Doxycycline / Macrolide / Resp FQ

if MRSA or Psuedo major or minor risk factors

MRSA- add vanco or linezolid

Psuedo- switch to ant psuedo b lactam

keep macrolide or doxycycline

Inpatient CAP treatment non-severe CAP

B lactam (unasyn/ceftriaxone) + Doxycycline / Macrolide

if MRSA or Psuedo major risk factors

MRSA- add vanco or linezolid

Psuedo- switch to ant psuedo b lactam

keep macrolide or doxycycline

Major MRSA risk

MRSA Infection or pos nasal swab

Major Pseudomonas Risk

Previous resp. Pseudomonas

Structural Lung disease

CAP treatment Duration

• Outpatient: 3–5 days

• Non-severe inpatient: 3–5 days

• Severe inpatient: at least 5 days

risk factors for developing MDR HAP and VAP.

• IV antibiotics within past 90 days

• Septic shock

• ARDS before VAP

• ≥5 days hospitalization before VAP

• Acute kidney replacement therapy before VAP

HAP and VAP Monotherapy potential drugs

• 
  

Cefepime	Yes	Covers Enterobacterales, Pseudomonas, and MSSA
Piperacillin-tazobactam	Yes	Covers the required backbone organisms
Meropenem/imipenem	Yes, but reserve	Appropriate for important MDR or ESBL risk
Levofloxacin	Sometimes	Has backbone activity, but beta-lactams are preferred

HAP and VAP drugs that cant be used in monotherapy

Aztreonam

Ciprofloxacin

Tobramycin

Ertapenem

Vancomycin/linezolid

Corticosteroids considered

• Severe bacterial CAP in the ICU.

• Patients with refractory septic shock who have a separate sepsis-based indication.

• Patients whose pneumonia triggered a COPD or asthma exacerbation, where steroids are indicated for the obstructive-airway disease.

POST CAP make sure to monitor

Clinical stability

• Temp <100.4

• HR < 100

• RR <24

• O2 Sat 90%

• SBP > 90

• Baseline mental status

Pneumonia Diagnosis

Clinically compatible findings

pulm image findings

Pneumonia Risk factors

Lifestyle

• Smoking

• Alcohol use

• Opiod use disorder

Meds

• Inhaled steroids in COPD

• Sedatives

• Acid supressants

• Antipsych meds

Common HAP/VAP Pathogens

Non MDRO (also seen in CAP)

• Strep Pnuem

• H influemzae

• Legionella

Enterobacterales

• E coli

• Klebsiella

• Enterobacter

MDRO (more common in HAP)

Psuedomonas

Acinetobacter

HAP

Onset Occurs > or = 48 hrs after hosptial admisssion

somtimes late onset 5+ days after admission

VAP

occurs > or = 48hrs after ventilation

HAP/VAP duration of therapy

Default = 7 days

HOWEVER

>7days

• S Aureus bacteremia

• lung abcess or empyema

Empiric therapy HAP/VAP Low mortality risk + no MDR risk factors

Backbone drug + Anti MRSA agent

Antipsuedo B lactam (preferred) or Levofloxacin

(Cefepime / Pip/Tazo)

+

Vanco/Linezolid

Empiric therapy HAP/VAP HIGH mortality risk + MDR risk factors

2 Anti PSuedo drugs from 2 diff classes (one beta lacta) + one Anti-MRSA agent

Antipsuedo B lactam (Cefepime / Pip/Tazo)

+Levofloxacin/ciprofloxacin or tobramycin

+Vanco or Linezolid

HAP high mortality risk

• Septic shock

• Ventilator support

HAP/VAP MDR Risk factors

HAP

• IV Abx in past 90 days

VAP

• IV Abx in past 90 days

• ARDS preceding VAP

• > or = 5 days hospitalized preceding VAP

• Acute KRT preceding VAP

Double Psuedomonas Coverage in HAP AND VAP

Required in structural lung disease

• Bronchiecstasis

• Cystic fibrosis

When to take peak level

60 mins after start of infusion

When to take trough

within 30 mins before next infusion

Steady state reached after

3 doses

Aminoglycoside levels in Hemodialysis

Hemodialysis:

Strategy	Timing
Pre-HD level	Immediately before dialysis
Post-HD level	At least 3 hours after dialysis ends

• Administer the aminoglycoside after HD.

• Manage like dose-by-level therapy.

• For course calculations, assume a four-hour HD session removes approximately 50%.

• Do not interpret a concentration drawn immediately after dialysis.

Aminoglycoside Loading dose considered when

• Serious or life-threatening infection

• Renal dysfunction, including CrCl below approximately 60 mL/min

• Dose-by-level therapy

• Any situation requiring immediate therapeutic exposure

Aminoglycosides

Gentamicin

Tobramycin

Amikacin

• Bind the 30S ribosomal subunit

• Mainly cover gram-negative organisms, including Pseudomonas

• Concentration-dependent killing

• PK/PD target = Cmax/MIC

• Have a long post-antibiotic effect

90% renally cleared

Aminoglycosides ADME

Absorption - poor oral absorption

Distribution - Primarily extracellular fluid; poor adipose, CSF, eye, and lung penetration

Metabolism- no clinically meaningful metabolism

Elimination- (90% eliminated by glomerular filtration

Think high peak for efficacy and low trough for safety: aminoglycosides are concentration-dependent and are eliminated almost entirely by the kidneys.

Aminoglycoside toxicities

• Nephrotoxicity

• Ototoxicity

• Vestibular toxicity

Common nephrotoxic antibiotics

Aminoglycosides / Vancomycin

Aminoglycoside Dosing Weight

Patient Weight	Dosing Weight
Actual weight < IBW	Actual body weight
IBW < actual weight <120% IBW	Actual body weight
Actual weight ≥120% IBW	Adjusted body weight

CrCl dosing weight

Patient Weight	Dosing Weight
Actual weight < IBW	Actual body weight
IBW < actual weight <120% IBW	Ideal body weight
Actual weight ≥120% IBW	Adjusted body weight

PK changes due to burn injury

Dehydrated = Decreased Vd

Given fluids = Increase Vd

Clearance increased